Ipsilateral vagotomy to unilaterally ovariectomized pre-pubertal rats modifies compensatory ovarian responses

The present study evaluates the participation of the vagus nerve in pre-pubertal rats with unilateral ovariectomy on puberty onset, and on progesterone, testosterone and estradiol serum levels, and the compensatory responses of the ovary. Unilateral vagotomy did not modify the onset of puberty in unilaterally ovariectomized rats. Ovulation rates of animals with the left vagus nerve sectioned and the left ovary in-situ was lower than in rats with only unilateral ovariectomy. Sectioning the left vagus to 32-day old rats with the left ovary in-situ resulted in lower compensatory ovarian hypertrophy than in rats with right unilateral ovariectomy. Twenty-eight or 32-day old animals with sectioning of the right vagus nerve and the right ovary in situ showed higher compensatory ovulation. Twenty-eight -day old rats with the right ovary in situ had higher progesterone and testosterone levels than animals of the same age with the left ovary in-situ. Compared to animals with the right ovary in situ, animals treated at 32-days of age, sectioning the ipsi-lateral vagus nerve resulted in higher progesterone levels. Higher progesterone levels were observed in 28- and 32 days old rats with the left ovary in situ and left vagus nerve sectioned. Thirty-two day old animals with the right ovary in situ and right vagus nerve sectioned had higher progesterone levels than rats of the same age with the left ovary in situ and left vagus nerve sectioned. Left vagotomy to 28-day old rats with the left ovary in situ resulted in higher testosterone levels, a reverse response to that observed in animals with sectioning of the right vagus and the right ovary in situ. Thirty-two day old rats with the left ovary in situ and left vagus nerve sectioned showed lower testosterone levels than animals without vagotomy and with the left ovary in situ

Could the clinical interpretability of subgroups detected using clustering methods be improved by using a novel two-stage approach?

Background: Recognition of homogeneous subgroups of patients can usefully improve prediction of their outcomes and the targeting of treatment. There are a number of research approaches that have been used to recognise homogeneity in such subgroups and to test their implications. One approach is to use statistical clustering techniques, such as Cluster Analysis or Latent Class Analysis, to detect latent relationships between patient characteristics. Influential patient characteristics can come from diverse domains of health, such as pain, activity limitation, physical impairment, social role participation, psychological factors, biomarkers and imaging. However, such 'whole person' research may result in data-driven subgroups that are complex, difficult to interpret and challenging to recognise clinically. This paper describes a novel approach to applying statistical clustering techniques that may improve the clinical interpretability of derived subgroups and reduce sample size requirements. Methods: This approach involves clustering in two sequential stages. The first stage involves clustering within health domains and therefore requires creating as many clustering models as there are health domains in the available data. This first stage produces scoring patterns within each domain. The second stage involves clustering using the scoring patterns from each health domain (from the first stage) to identify subgroups across all domains. We illustrate this using chest pain data from the baseline presentation of 580 patients. Results: The new two-stage clustering resulted in two subgroups that approximated the classic textbook descriptions of musculoskeletal chest pain and atypical angina chest pain. The traditional single-stage clustering resulted in five clusters that were also clinically recognisable but displayed less distinct differences. Conclusions: In this paper, a new approach to using clustering techniques to identify clinically useful subgroups of patients is suggested. Research designs, statistical methods and outcome metrics suitable for performing that testing are also described. This approach has potential benefits but requires broad testing, in multiple patient samples, to determine its clinical value. The usefulness of the approach is likely to be context-specific, depending on the characteristics of the available data and the research question being asked of it

Innovating the didactical methodologies applied in Universities through Second Life and Practice Firm: case study

The paper analyses and discusses Second Life and Practice Firm as two innovative methodologies used in education considering the recent experiences carried out by Bologna University - Forlì School of Economics, Management and Statistics. Although fast advancements in ICTs frontier for teaching and learning and their criticisms, Higher Education Institutions increasingly used Second Life and Practice firm to test new didactical methodologies. All these topics will be discussed by analysing the experiences in progress carried out by Bologna University - Forlì School of Economics, Management and Statistics in the usage of Second Life, started in 2008, and of Practice Firm through which Perting, the first simulated firm established in an Italian University, operates in consulting services and ICT goods trade. The research question refers to: how we can connect Practice Firm and Second Life in the learning transfer of knowledge, capacities and skills? The paper outlines the main features and implications of these didactical methodologies and how they can be connected for improving the educational process undertaken by Universities

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Epidermolysa bullosa in Danish Hereford calves is caused by a deletion in LAMC2 gene

BACKGROUND Heritable forms of epidermolysis bullosa (EB) constitute a heterogeneous group of skin disorders of genetic aetiology that are characterised by skin and mucous membrane blistering and ulceration in response to even minor trauma. Here we report the occurrence of EB in three Danish Hereford cattle from one herd. RESULTS Two of the animals were necropsied and showed oral mucosal blistering, skin ulcerations and partly loss of horn on the claws. Lesions were histologically characterized by subepidermal blisters and ulcers. Analysis of the family tree indicated that inbreeding and the transmission of a single recessive mutation from a common ancestor could be causative. We performed whole genome sequencing of one affected calf and searched all coding DNA variants. Thereby, we detected a homozygous 2.4 kb deletion encompassing the first exon of the LAMC2 gene, encoding for laminin gamma 2 protein. This loss of function mutation completely removes the start codon of this gene and is therefore predicted to be completely disruptive. The deletion co-segregates with the EB phenotype in the family and absent in normal cattle of various breeds. Verifying the homozygous private variants present in candidate genes allowed us to quickly identify the causative mutation and contribute to the final diagnosis of junctional EB in Hereford cattle. CONCLUSIONS Our investigation confirms the known role of laminin gamma 2 in EB aetiology and shows the importance of whole genome sequencing in the analysis of rare diseases in livestock

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

Worldwide use of the first set of physical activity Country Cards: The Global Observatory for Physical Activity - GoPA!

Background: The work of The Global Observatory for Physical Activity-GoPA! is the first global effort to compile standardized country-level surveillance, policy and research data for physical activity in order to better understand how countries and regions address promoting physical activity. GoPA! developed standardized country-specific physical activity profiles (“Country Cards”) to summarize country-level data through 2013. The aim of this study was to assess use of the Country Cards, identify the factors associated with their use, and develop recommendations for supporting country-level physical activity promotion. Methods: Cross sectional internet-based survey conducted between August–October 2016. Target study participants were national physical activity leaders and advocates in academia, government and practice from the GoPA! countries, and members of the International Society of Physical Activity and Health. A Country Card use composite score was created based on the diversity and frequency of use. Statistical analyses on the associations between the composite score and respondent characteristics, country characteristics, barriers and opinions were conducted (including descriptive analyses and a logistic regression with robust standard errors). Results: One hundred forty three participants from 68 countries completed the survey. Use of the Country Cards was associated with being part of the GoPA! network, knowing about the Country Cards, and on the stage of country capacity for physical activity promotion. Country Card knowledge varied by country income group, region and the country specific context. More diverse and frequent use of the cards (highest tertile of the composite score for use) was associated with: 1. Being a country contact vs general participant (OR 18.32–95% CI 5.63–59.55, p = 0.002), and 2. Collaborating with a government representative working in NCDs on a monthly or more frequent contact vs less frequent contact (OR 3.39–95% CI 1.00–11.54, P < 0.05). Conclusions: For the Country Cards to have a broader impact, GoPA! will need to widen its reach beyond the academic sector. With further refinement of the cards, and training in their implementation, they could be an important tool for advancing country capacity for contextually-relevant strategies, actions and timelines for PA promotion